CZ169797A3 - Aromates substituted by benzyloxy group and their use as fungicidal and insecticidal agents - Google Patents

Abstract

Compounds with fungicidal and insecticidal properties having formula <CHEM> wherein A is N or CH; V is O or NH; m and n are independently 0 or 1 provided that m + n is not 2, and U and W are independently O or N; such that when U and W are both N and n is 0 and m is 1, the bond between the 1 and 5 atoms is a double bond and the bond between the C3-C4 atoms is a single or double bond, and when n is 1 and m is 0, the bond between the 2 and 3 atoms is a double bond and the bond between the C4-C5 atoms is a single or double bond; and that when U is O and W is N and n=m=0, the bond between the 1 and 5 atoms is a double bond and the bond between the C3-C4 atoms is a single or double bond; and that when U is N and W is O and n=m=0, the bond between the 2 and 3 atoms is a double bond and the bond between the C4-C5 atoms is a single or double bond; X is independently selected from hydrogen, halo, (C1-C4)alkyl, and C1-c4)alkoxy; R is independently selected from hydrogen, (C1-C12)alkyl, halo(C1-C12)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl,(C1-C12)alkoxy(C1-C12)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C4)alkyl, aryl, aralkyl, heterocyclic;and R1 is independently selected from hydrogen, (C1-C6)alkyl, and aryl; and Z is selected from (C1-C6)alkyl, halo(C1-C6)allcyl, (C3-C7) cycloalkyl, (C3-C7)cycloalkyl(C1-C4)alkyl, aryl and aralkyl.

Description

Benzyloxy substituted aromatics and their use as fungicides and insecticides

Technical field

The present invention relates to a group of benzyloxy substituted phenyl compounds, compositions containing them and methods for controlling, i.e., controlling fungi and insects, using fungitoxic and insecticidal amounts of these compounds.

It is known that propanoic acid and the oximes of ethers, certain benzyloxy substituted phenyl compounds, are preferred as fungicides. Substitution of the phenyl cyclic chain with certain heterocycles is known in the art (see, eg, US Patent No. 5,185,342).

SUMMARY OF THE INVENTION

We have discovered phenyl derivatives having a five-membered cyclic heterocyclic chain. These novel compositions also have fungicidal and insecticidal properties.

The novel benzyloxy substituted phenyl compounds of this invention have the general Formula I

O • · · · ···· · ··· ···

- 2 where:

A is N or CH; V is O or NH;

m and n are independently 0 or 1, provided that m + n is not 2 and U and W are independently O or N;

so when U and W are both NanjeOamjel, the bond between

The 1st and 5th atoms are double bonds and the bond between the C3C4 atoms is a single or double bond and when n is 1 and m is 0, the bond between the 2nd and 3rd atoms is a double bond and the bond between atoms

C4-CB is a single or double bond;

and that when U is O and W is N and n = m = 0, the bond between the 1st and 5th atoms is a double bond and the bond between the C3-C4 atoms is a single or double bond;

and that when U is N and W is Oan = m = 0, the bond between the 2 and 3 atoms is a double bond and the bond between the C4-C5 atoms is a single or double bond;

X is independently selected from hydrogen, halo, (C 1 -C 4) alkyl and (C 1 -C 4) alkoxy;

R is independently selected from hydrogen, (C 1 -C 12) alkyl, halo (C 1 -C 12) alkyl, (C 2 -C 6) alkenyl, (C 2 -C 6 alkynyl, (C 1 -C 12) alkoxy (C 1 -C 12) alkyl, ( C3-C2) cycloalkyl, (C3-C2) cycloalkyl (C1-C4) alkyl, aryl, aralkyl, heterocyclic;

R 1 is independently selected from hydrogen, (C 1 -C 6) alkyl and aryl;

Z is selected from (C 1 -C 6) alkyl, halo (C 1 -C 6) alkyl, (C 3 -C 7) cycloalkyl, (C 3 -C 7) cycloalkyl (C 1 -C 4) alkyl, aryl, aralkyl.

The above-mentioned (C 1 -C 12) alkyl, (C 1 -C 12) alkoxy, (C ₂ -C ₆ ) alkenyl, (C ₂ -C ₆ ) alkynyl and (C ₃ -C ₂ ) cycloalkyl groups may be optionally substituted with up to three substituents selected from halogen, nitro, trihalomethyl and cyano.

The term alkyl includes both branched and unbranched chains of alkyl groups having 1 to 12 carbon atoms. Typical alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, isooctyl, nonyl, decyl, undecyl, dodecyl and the like.

The term haloalkyl refers to alkyl groups substituted with 1 to 3 halogens.

The term alkenyl refers to unsaturated hydrocarbon groups having a double bond, unbranched and branched having a chain length of 2 to 12 carbon atoms and 1 or 2 double bonds. The term haloalkenyl refers to alkenyl groups, substituted with 1 to 3 halogen atoms.

The term alkynyl refers to unsaturated hydrocarbon groups, unbranched or branched, having a chain length of 2 to 12 carbon atoms and 1 or 2 triple bonds.

The term cycloalkyl refers to saturated cyclic chain systems having 3 to 7 carbon atoms.

The term aryl is to be understood as phenyl or naphthyl which may be further substituted by up to three substituents selected from halogen, cyano, nitro, trihalomethyl, phenyl, phenoxy, (C 1 -C 4) alkyl, (C 1 -C 4) alkylthio, (C 1 -C 4) alkyl. -C4) alkylsulfoxide (C1-C4) alkoxy and halo (C1-C4) alkyl.

Typical aryl substituents include, but are not limited to, 4-chlorophenyl, 4-fluorophenyl, 4-bromophenyl, 2-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,4-dibromophenyl, 3,5-difluorophenyl, 2,4,6-trichlorophenyl, 4-methoxyphenyl, 2-chloronaphthyl, 2,4-dimethoxyphenyl, 4- (trifluoromethyl) phenyl and 2-iodo-4-methylphenyl.

The term heterocyclic refers to substituted or unsubstituted 5- or 6-membered unsaturated cyclic chains containing one, two or three heteroatoms, preferably one or two heteroatoms, selected from oxygen, nitrogen and sulfur; or is a bicyclic unsaturated ring system containing up to 10 atoms including one heteroatom selected from oxygen, nitrogen and sulfur. Examples of heterocycles include, but are not limited to, 2-, 3- or 4-pyridinyl, pyrazinyl, 2-, 4- or

5-pyrimidinyl, pyridazinyl, triazolyl, imidazolyl, 2- or

«« 999 ·

3-thienyl, 2- or 3-furyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, quinolyl and isoquinolyl. The heterocyclic chain may be optionally substituted with up to 2 substituents independently selected from (C 1 -C 4) alkyl, halogen, cyano, nitro and trihalomethyl.

The term aralkyl is used to describe a group in which the alkyl chain has 1 to 10 carbon atoms and may be a branched or unbranched chain, preferably an unbranched chain, with a terminal aryl moiety as defined above. Typical aralkyl groups include, but are not limited to, optionally substituted benzyl, phenethyl, fenpropyl and phenobutyl groups. Typical benzyl groups are 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 4-trifluoromethylbenzyl, 2,4-dichlorobenzyl, 2,4-dibromobenzyl, 2- methylbenzyl, 3-methylbenzyl and 4-methylbenzyl. Typical phenethyl groups are 2- (2-chlorophenyl) ethyl, 2- (3-chlorophenyl) ethyl, 2- (4-chlorophenyl) ethyl, 2- (2-fluorophenyl) ethyl, 2- (3-fluorophenyl) ethyl ,

2- (4-fluorophenyl) ethyl, 2- (2-methylphenyl) ethyl, 2- (3-methylphenyl) ethyl, 2- (4-methylphenyl) ethyl, 2- (4-trifluoromethylphenyl) ethyl, 2- (2- methoxyphenyl) ethyl, 2- (3-methoxyphenyl) ethyl,

2- (4-methoxyphenyl) ethyl, 2- (2,4-dichlorophenyl) ethyl, 2- (3, 4-methoxyphenyl) ethyl;

5-dimethoxyphenyl) ethyl. Typical phenopropyl groups are

3-phenylpropyl, 3- (2-chlorophenyl) propyl, 3- (3-chlorophenyl) propyl,

3- (4-chlorophenyl) propyl 3- (2,4-dichlorophenyl) propyl, 3- (2-fluorophenyl) propyl, 3- (3-fluorophenyl) propyl, 3- (4-fluorophenyl) propyl,

3- (2-methylphenyl) propyl, 3- (3-methylphenyl) propyl, 3- (4-methylphenyl) propyl, 3- (2-methoxyphenyl) propyl, 3- (3-methoxyphenyl) propyl, 3- (4- methoxyphenyl) propyl, 3- (4-trifluoromethylphenyl) propyl, 3- (2,4-dichlorophenyl) propyl, and 3- (3,5-dimethoxyphenyl) propyl. Typical phenobutyl groups are 4-phenylbutyl,

4- (2-chlorophenyl) butyl, 4- (3-chlorophenyl) butyl, 4- (4-chlorophenyl) butyl, 4- (2-fluorophenyl) butyl, 4- (3-fluorophenyl) butyl,

4- (4-fluorophenyl) butyl, 4- (2-methylphenyl) butyl, 4- (3-methylphenyl) butyl, 4- (4-methylphenyl) butyl, 4- (2,4-dichlorophenyl) •

5-butyl, 4- (2-methoxyphenyl) butyl, 4- (3-methoxyphenyl) butyl and 4- (4-methoxyphenyl) butyl.

Halogen or halo means that it contains iodine, fluorine, bromine and chlorine groups.

Due to the C = C or C = N double bonds, the novel compounds of formula (I) can be obtained as an E / Z isomer mixture in the preparation. These isomers can be separated into individual components by conventional means. The pyrazolines and isoxazolines of formula I can be prepared as cis and trans isomer mixtures by preparation. These isomers are separated into individual components by conventional means. Both the individual isomeric compounds and mixtures thereof are subject of the invention and are useful as fungicides.

Preferred embodiments of the invention are compounds, enantiomorphs, salts and complex compounds of formula I when H is (C 1 -C 6) alkyl; phenyl substituted preferably with one or two substituents independently selected from halo, trihalomethyl, cyano, (C 1 -C 6) alkyl, (C 1 -C 6) alkylthio, (C 1 -C 4) alkoxy; or phenyl, R 1 is H, wherein the OCH 2 (2-substituted phenyl) group is bonded at the meta position to the 5-membered ring chain substituent of the phenyl chain as shown in Formula I.

H _S C (V) OC

A-OCH3 (I ')

Even more preferred embodiments of the invention are compounds, enantiomorphs, salts and complex compounds of formula I when X is hydrogen and R is haloenyl and A is CH and V is O. Preferred geometry when A is CH or N is E isomer .

Typical compounds encompassed by this invention of Formula I include those shown in Table 1 of Formulas II, III and IV wherein X = H, R 1 = H, U and W are N and n = 0 and m = 1.

H ₃ C (V) OC A-OCH 3

H ₃ C (V) OC • a-s ₃ (II) (III) (IV)

Table 1

merge number R formula of AND IN 1.01 Ar II CHa CH O 1.02 Ar III CHa CH 0 1.03 Ar IV ch ₃ CH O 1.04 4 — Cl (Ar) II CHa CH O 1.05 4-Cl III CH3 CH O 1.06 4 — Cl (Ar) IV CHa CH O 1.07 4-F II CHa CH O 1.08 4-F III CHa CH O 1.09 4-F IV CHa CH O 1.10 _2-CH3 (Ar) II CHa CH O

• · · · · · · · · · · · · · · · · · · · · · ·

- Ί Table 1 - continued

R formula 2 AND IN 2-CH (Ar) III CHa CH O 2-CH (Ar) IV CHa CH O 4-CH (Ar) II CHa CH O 4-CH 3 (Ar) III CHa CH O 4-CH (Ar) IV CHa CH O 4-CF3 II CHa CH O 2,4-Cl II CHa CH O CHa II CHa CH O CHz CHa II CHa CH O CHz CHz CHa II CHa CH O CH (CH3) ₂ II CHa CH O CH2 (CH2) and CH2 II CHa CH O CH 2 (CH 2) ₄ CHa II CHa CH O CH2CH (CHa) ₂ II CHa CH O CH (CHa) CH 2 CH ₃ II CHa CH O C (CH3) a II CHa CH O CH 2 C (CH 3) 3 II CHa CH O CH 2 CH 2 CH 2 CH 2 II CHa CH 0 C (CHa) 2 CH 2 CHa II CHa CH O cf ₃ II CHa CH O CF ₂ CF ₃ II CHa CH O CH 2 CF ₃ II CHa CH O CH = CH ₂ II CHa CH O cyclopropy1 II CHa CH 0 cyclopenty1 II CHa CH O cyclohexyl II CHa CH O CHzOCHa II CHa CH O CHz OCHz CHa II CHa CH O CHz CHz OCOAr II CHa CH O CHz OCHz Ar II CHa CH O 2-pyridyl II CHa CH O 3-pyridy1 II CHa CH 0

Table 1 - Completion

merge number (B) formula 2 AND IN 1.43 2-pyrimides1 II CHa CH O 1.44 4-pyrimides 1 II ch ₃ CH O 1.45 2-thienyl II CHa CH O 1.46 3-thienyl II CHa CH O 1.47 2-naphthyl II CHa CH O 1.48 Ar II Cz H © CH O 1.49 4 — Cl (Ar) II Cz H © CH O 1.50 CHa II Cz H © CH O 1.51 CHz CHa II CzH © CH O 1.52 CH 2 CH 2 CH ₃ II Cz H © CH O 1.53 CH (CHa) 2 II Cz H5 CH O 1.54 CH 2 (CH 2) ₃ CHa II Cz H5 CH O 1.55 CHzCHíCHg) ₂ II Cz Hs CH O 1.56 C (CH3) ₃ II Cz H5 CH O 1.57 Ar III 4 — Cl (Ar) CH O 1.58 Ar II CH ₂ CH ₂ CH ₂ CH O 1.59 CHa II CHz CHz CHa CH O 1.60 CH 2 CH 2 CH ₃ II CHz CHz CHa CH 0 1.61 CH 2 CH 2 z II CHz CHz CHa CH O 1.62 CH 2 (CH 2) ₃ CHa II CHz CHz CHa CH O 1.63 CH ₂ CH (CH ₃ ) ₂ II CHz CHz CHa CH O 1.64 C (CH3) ₃ II CHz CHz CHa CH O 1.65 2-pyridyl II CHz CHz CHa CH O 1.66 3-pyridyl II CHz CHz CHa CH O 1.67 4-pyrimides II CHz CHz CHa CH O 1.68 2-thienyl II CHz CHz CHa CH O 1.69 3-thienyl II CHz CHz CHa CH O 1.70 2-naphthyl II CHz CHz CHa CH O

Other typical compounds described by this invention are described in the following tables.

Compounds of formulas XI,

Compounds of formulas II,

Compounds of formulas II,

Compounds of formulas II,

Compounds of formulas II,

Compounds νζοι-οβ II,

- 9 Table 2

2.1 to 2.47 are compounds of Table 1, general III, IV, wherein 2 is Ar.

Table 3

3.1 to 3.47 are compounds of Table 1, general III, IV, wherein Z is CH 2 Ar.

Table 4

4.1 to 4.47 are compounds of Table 1, general III, IV, wherein Z is CH ₂ CF ₃ .

Table 5

5.1 to 5.47 are compounds of Table 2, General III, IV, wherein V is O and A is N.

Table 6

6.1 to 6.47 are compounds of Table 2, General III, IV, wherein V is NH and A is N.

Table 7

7.1 to 7.47 are compounds of Table 3, General III, IV, wherein V is O and A is N.

- 10 Table 8

Compounds 8.1 to 8.47 are compounds of Table 3 of Formulas II, III, IV wherein V is NH and A is N.

Table 9

Compounds 9.1 to 9.47 are compounds of Table 4 of Formulas II, III, IV, wherein V is O and A is N.

Table 10

Compounds 10.1 to 10.47 are compounds of Table 4 of Formulas II, III, IV wherein V is NH and A is N.

Typical compounds within the scope of this invention of Formula I include those of Table 11 of Formula V,

VI and VII, where X = H, R 1 = H, U and W are Nan = 1 and m = 0.

R

(VII) (V) (VI)

- 11 Table 11

siouí ;. number R formula 2 AND IN 11.01 Ar IN CHa CH 0 11.02 Ar VI CH ₃ CH O 11.03 Ar VII CHa CH O 11.04 4-C1 IN CHa CH 0 11.05 4 — Cl (Ar) VI CHa CH O 11.06 4 — Cl (Ar) VII CHa CH O 11.07 4-F IN CH3 CH O 11.08 4-F VI CHa CH O 11.09 4-F VII CHa CH O 11.10 2-CH (Ar) IN CHa CH O 11.11 _2-CH3 (Ar) VI CHa CH O 11.12 2 — CH3 (Ar) VII CHa CH O 11.13 _4-CH3 (Ar) IN CHa CH 0 11.14 4-CH 3 (Ar) VI CHa CH O 11.15 4-CH 3 (Ar) VII CHa CH 0 11.16 4 — CF ₃ (Ar) in CHa CH O 11.17 2,4-Cl in CHa CH O 11.18 CH3 in CHa CH O 11.19 CHz CHa in CHa CH O 11.20 CHz CHz CHa in CHa CH O 11.21 CH (CH 3) ₂ in CHa CH 0 11.22 CH 2 (CH 2) ₃ CH 3 in CHa CH O 11.23 CH2 (CH2) 4CH3 in CHa CH O 11.24 CH 2 CH (CH 3) 2 in CHa CH O 11.25 CH (CHa) CH2 CHa in CHa CH O 11.26 C (CH3) ₃ in CHa CH O 11.27 CH 2 C (CH ₃ ) ₃ in CHa CH O 11.28 CH (CH ₃ ) CH 2 CH 2 CH ₃ in CHa CH O 11.29 C (CHa) 2 CH ₂ CH ₃ in CHa CH 0 11.30 CF ₃ in CHa CH O 11.31 CF ₂ CF ₃ in CHa CH 0 11.32 CH 2 CF ₃ in CHa CH 0

• · · ·

- 12 Table 11 - continued

s1ouč. number R formula 2 AND IN 11.33 CH = CH ₂ IN ch ₃ CH O 11.34 cyclopropyl IN CH ₃ CH O 11.35 cyclopenty1 IN CHa CH O 11.36 cyclohexyl IN CHa CH 0 11.37 CH 2 OCH ₃ IN CHa CH O 11.38 CH 2 OCH 2 CH ₃ IN CHa CH O 11.39 CHz CHz OCOAr IN CHa CH O 11.40 CHz OCHz Ar IN CHa CH O 11.41 2 — py r-icly 1 IN CHa CH O 11.42 3-pyridy1 IN CHa CH O 11.43 2-pyrimidyl IN CHa CH O 11.44 4-pyrimidyl IN CHa CH O 11.45 2-thienyl IN CHa CH O 11.46 3-thienyl IN CHa CH O 11.47 2 — naphthyl1 IN CHa CH O 11.48 Ar IN CzH ₅ CH O 11.49 4 — Cl (Ar) IN CzH ₅ CH O 11.50 CH ₃ IN CzHs CH O 11.51 CHz CHa IN CzHs CH O 11.52 CHz CHz CHa IN CzHb CH O 11.53 CH ₂ CH ₂ ) IN Cz Hs CH O 11.54 CH 2 (CH 2) and CH ₃ IN Cz Hs CH O 11.55 CH 2 CH (CH 3) 2 IN C2H5 CH 0 11.56 C (CH3) a IN C2 Hs CH O 11.57 Ar VI 4 — Cl (Ar) CH O 11.58 Ar IN CHz CHz CHa CH 0 11.59 CHa IN CHz CHz CHa CH O 11.60 CHz CHz CHa in CHz CHz CHa CH O 11.61 CHCCH a) in CHz CHz CHa CH O 11.62 CH 2 (CH 2) ₃ CH ₃ in CHz CHz CHa CH O 11.63 CH 2 CH (CH 3) 2 in CHz CHz CHa CH 0 11.64 C (CH3) ₃ in CHz CHz CHa CH O

·· ·

- 13 Table 11 - Completion

s1ouč. number TO formula 2 AND IN 11.65 2-pyridyl IN CH 2 CH 2 CH 3 CH 0 11.66 3-pyridyl IN CH 2 CH 2 CH ₃ CH O 11.67 4-pyrimides IN CHz CHz CHa CH O 11.68 2-thienyl IN CHz CHz CHa CH O 11.69 3-thienyl IN CHz CHz CHa CH 0 11.70 2-na1ty1 IN CHz CHz CHa CH O

Other typical compounds described by this invention are described in the following tables

Table 12

Compounds 12.1 to 12.47 are compounds of Table 11 of Formulas V, VI, VII, wherein 2 is Ar.

Table 13

Compounds 13.1 to 13.47 are compounds of Table 11 of Formulas V, VI, VII, wherein 2 is CH 2 Ar.

Table 14

Compounds 14.1 to 14.47 are compounds of Table 11 of Formulas V, VI, VII, wherein 2 is CH 2 CF 3.

Table 15

Compounds 15.1 to 15.47 are compounds of Table 12 of Formulas V, VI, VII, wherein V is O and A is N.

»· · · ·

• ·

Table 16

Compounds 16.1 to 16.47 are compounds of Table 12 of Formulas V, VI, VII, wherein V is NH and A is N.

Table 17

Compounds 17.1 to 17.47 are compounds of Table 13 of Formulas V, VI, VII, wherein V is O and A is N.

Table 18

Compounds 18.1 to 18.47 are compounds of Table 13 of Formulas V, VI, VII, wherein V is NH and A is N.

Table 19

Compounds 19.1 to 19.47 are compounds of Table 14 of Formulas V, VI, VII, wherein V is O and A is N.

Table 20

Compounds 20.1 to 20.47 are compounds of Table 14 of Formulas V, VI, VII, wherein V is NH and A is N.

Typical compounds of this invention of Formula I include those of Table 21 of Formulas VIII, IX and X, wherein X = H, R 1 = H, U and W are N and n = 0 and m = 1.

H, U and W are N and n • 9 99 9

(VIII) (IX) &)

Table 21

merge number R formula of AND IN 21.01 Ar VIII CHa CH O 21.02 Ar IX CHa CH O 21.03 Ar X CHa CH 0 21.04 4 — Cl (Ar) VIII CHa CH O 21.05 4 — Cl (Ar) IX CHa CH O 21.06 4 — Cl (Ar) X CHa CH O 21.07 4-F VIII CHa CH O 21.08 4-F IX CHa CH O 21.09 4-F X CHa CH O 21.10 2-CH (Ar) VIII CHa CH O 21.11 2-CH (ftr) IX CHa CH O 21.12 _2-CH3 (Ar) X CHa CH O 21.13 4 — CHg (Ar) VIII CHa CH O 21.14 4-CH (Ar) IX CHa CH O 21.15 4 — CHa (Ar) X CHa CH O 21.16 4-CFa (Ar) VIII CHa CH O 21.17 2,4-Cl VIII CHa CH 0 21.18 CHa VIII CHa CH O 21.19 CHz CHa VIII CHa CH 0

9 9

- 16 Table 21 - continuation of comp. R formula Z A V number

21.20 CHz CHz CHa VIII CHa CH O 21.21 CH ₂ CH ₂ ) ₂ VIII CH3 CH 0 21.22 CH 2 (CH 2) and CH 3 VIII CHa CH O 21.23 CH 2 (CH 2) ₄ CHa VIII CHa CH O 21.24 CH 2 CH (CH ₃ ) ₂ VIII CHa CH O 21.25 CH (CHa) CH2 CHa VIII CHa CH O 21.26 C (CH3) ₃ VIII CHa CH O 21.27 CH 2 C (CH 3) a VIII CHa CH O 21.28 CH (CHa) CH2 CH2 CH2 VIII CHa CH O 21.29 C (CH 2 J 2 CH 2 CH 2 VIII CHa CH O 21.30 CFa VIII CHa CH O 21.31 CFz CFa VIII CHa CH O 21.32 CH 2 CFa VIII CHa CH 0 21.33 CH = CH ₂ VIII CHa CH O 21.34 cyclopropy1 VIII CHa CH O 21.35 cyclopentyl VIII CHa CH O 21.36 cyclohexyl VIII CHa CH O 21.37 CHzOCHa VIII CHa CH O 21.38 CHz OCHz CHa VIII CHa CH O 21.39 CHz CHz OCOAr VIII CHa CH 0 21.40 CHz OCHz Ar VIII CHa CH 0 21.41 2-pyridyl VIII CHa CH O 21.42 3-pyridyl VIII CHa CH O 21.43 2-pyrimides1 VIII CHa CH O 21.44 4-pyrimides1 VIII CHa CH O 21.45 2-thienyl VIII CHa CH O 21.46 3-thienyl VIII CHa CH O 21.47 2-na1ty1 VIII CHa CH O 21.48 Ar VIII Ar CH 0 21.49 4-Cl VIII Ar CH O 21.50 CHa VIII Ar CH 0 21.51 CHz CHa VIII Ar CH O

·· »·· ·

Table - 17 - 21 - completion AND IN merge number (B) formula of 21.52 CHz CHz CHa VIII Ar CH O 21.53 CHÍCHa) from VIII Ar CH O 21.54 CH2 (CH2) and CH2 VIII Ar CH O 21.55 CH 2 CH (CH ₃ ) ₂ VIII Ar CH 0 21.56 C (CH3) ₃ VIII Ar CH O 21.57 Ar VIII CHz Ar CH O 21.58 4-Cl VIII CHz Ar CH 0 21.59 CHa VIII CHz Ar CH O 21.60 CHz CHz CHa VIII CHz Ar CH 0 21.61 CH (CHa) 2 VIII CHz Ar CH O 21.62 CH 2 (CH 2) ₃ CHa VIII CHz Ar CH O 21.63 CH2CH (CHa) ₂ VIII CHz Ar CH O 21.64 C (CH3) a VIII CHz Ar CH O 21.65 Ar VIII CFz CFa CH 0 21.66 4-Cl VIII CFz CFa CH O 21.67 CHa VIII CFz CFa CH O 21.68 CHz CHz CHa VIII CFz CFa CH O 21.69 C (CH3) a VIII CFz CFa CH O 21.70 2-thienyl VIII CFz CFa CH O Next typical compounds described herewith invention. are

described in the following tables

Table 22

Compounds 22.1 to 22.70 are compounds of Table 19 of formulas VIII, IX, X, wherein V is O and A is only N.

Table 23

Compounds 23.1 to 23.70 are compounds of Table 19 of Formulas VIII, IX, X, wherein V is NH and A is N.

· * · * * * * * * · · · · · · · · · · · · · · · · · · · · · * »

Typical compounds of this invention of Formula I include those of Table 24 of Formulas XI, XII, and XIII, wherein X = H, R 1 = H, U, and W are Nan = l and m = O.

R

(XII) ^(χπι)

Table 24

merge number R formula of AND IN 24. 01 Ar XI ch ₃ CH O 24. 02 Ar XII ch ₃ CH O 24. 03 Ar XIII Cf-fe CH O 24. 04 4 — Cl (Ar) XI ch ₃ CH 0 24. 05 4 — Cl (Ar) XII ch ₃ CH O 24. 06 4 — Cl (Ar) XIII ch ₃ CH O 24. 07 4-F XI ch ₃ CH 0 24. 08 4-F XII ch ₃ CH O 24. 09 4-F XIII ch ₃ CH O 24. 10 2-CH (Ar) XI CHs CH 0 24. 11 2 — CH ₃ (Ar) XII ch ₃ CH O 24. 12 _2-CH3 (Ar) XIII ch ₃ CH O 24.13 4-CH 3 (Ar) XI CH3 CH O 24.14 4-CH (Ar) XII ch ₃ CH 0 24.15 4-CH (Ar) XIII CH3 CH 0

• · · · · · · · · · ·

- 19 Table 24 - continued

merge number R formula of AND IN 24. 16 4-CF ₃ XIII CHa CH O 24. 17 2,4 — Cl (Ar) XIII CHa CH O 24. 18 CHa XIII CHa CH O 24. 19 CHz CHa XIII CHa CH 0 24. 20 CH 2 CH ₂ CHa XIII CHa CH O 24. 21 CH (CHa) 2 XIII CHa CH O 24. 22 CH 2 (CH 2) 3 CHa XIII CHa CH O 24. 23 CH2 (CH2) 4CHa XIII CHa CH O 24. 24 CH2CH (CHa) ₂ XIII CHa CH O 24. 25 CH ₂ CH ₂ CH ₂ XIII CHa CH O 24. 26 C (CH3) ₃ XIII CHa CH O 24. 27 CH 2 C (CHa) a XIII CHa CH 0 24. 28 CH ₂ CH ₂ CH ₂ CH ₂ CH XIII CHa CH O 24. 29 C (CHa) from CH 2 CHa XIII CHa CH O 24. 30 CFa XIII CHa CH O 24.31 CFz CFa XIII CHa CH O 24. 32 CH 2 CFa XIII CHa CH O 24. 33 CH = CH 2 XIII CHa CH O 24. 34 cyclopropy1 XIII CHa CH O 24. 35 cyclopentyl XIII CHa CH O 24. 36 cyclohexyl XIII CHa CH O 24. 37 CH ₂ OCH ₃ XIII CHa CH O 24. 38 CHz OCHz CHa XIII CHa CH O 24. 39 CHz CHz OCOAr XIII CHa CH O 24.40 CHz OCHz Ar XIII CHa CH O 24.41 2-pyridyl XIII CHa CH O 24. 42 3-pyridy1 XIII CHa CH O 24.43 2 — pyrimides1 XIII CHa CH O 24. 44 4-pyrimidyl XIII CHa CH O 24. 45 2-thienyl XIII CHa CH O 24.46 3-thienyl XIII CHa CH O 24.47 2-naphthyl XIII CHa CH O

·· ···· · · · · · · ·

- 20 Table 24 - Completion

merge number R formula of AND IN 24.48 Ar XIII Ar CH O 24.49 4 ~ Cl XIII Ar CH O 24. 50 CHa XIII Ar CH O 24. 51 CHz CHa XIII Ar CH 0 24. 52 CHz CHz CHa XIII Ar CH O 24. 53 CHÍCHa) from XIII Ar CH O 24. 54 CH 2 (CH 2) ₃ CHa XIII Ar CH 0 24. 55 CH ₂ CH (CH ₃ ) ₂ XIII Ar CH O 24. 56 C (CH 3) ₃ XIII Ar CH O 24. 57 Ar XIII CHz Ar CH O 24. 58 4 — Cl (Ar) XIII CHz Ar CH O 24. 59 CHa XIII CHz Ar CH O 24. 60 CHz CHz CHa XIII CHz Ar CH O 24. 61 CH (CH 3) ₂ XIII CHz Ar CH O 24. 62 CH2 (CH2) and CH2 XIII CHz Ar CH 0 24. 63 CH2CH (CHa) 2 XIII CHz Ar CH O 64 C (CH3) ₃ XIII CHz Ar CH O 24. 65 Ar XIII CFz CFa CH O 24. 66 4 — Cl (Ar) XIII CFz CFa CH O 24. 67 CHa XIII CFz CFa CH O 24. 68 CHz CHz CHa XIII CFz CFa CH 0 24. 69 C (CH3) a XIII CFz CFa CH O 24. 70 2-thienyl XIII CFz CFa CH O Next described in typical compounds described in the following tables herewith invention. are

Table 25

Compounds 25.1 to 25.70 are compounds of Table 24 of Formulas XI, XII, XIII, wherein V is O and A is N.

·· ····

- 21 Table 26

Compounds 26.1 to 26.70 are compounds of Table 24 of Formulas XI, XII, XIII, wherein V is NH and A is N.

Typical compounds of this invention of Formula I include those of Table 27 of Formulas XIV, XV and XVI, wherein X = H, R 1 = H, U is O, W is N, and n m are 0.

(XV) (XV)

Table 27

merge number R formula AND IN 27.01 Ar XIV CH O 27.02 Ar XV CH O 27.03 Ar XVI CH O 27.04 4-Cl XIV CH 0 27.05 4 — Cl (Ar) XV CH O 27.06 4 — Cl (Ar) XVI CH 0 27.07 4-F XIV CH O 27.08 4-F XV CH O 27.09 4-F XVI CH O

• · · · · ·

- 22 Table 27 - continued

s1ouč. number (B) formula AND IN Oct / 27 2-CH (Ar) XIV CH O 27.11 2-CH (Ar) XV CH O 27.12 2-CH (Ar) XVI CH O 27.13 4-CH (Ar) XIV CH O 27.14 _4-CH3 (Ar) XV CH O 27. 15 4 — CHa (Ar) XVI CH O 27.16 4-CF3 XIV CH 0 27.17 2,4 — Cl (Ar) XIV CH O 27.18 CH3 XIV CH 0 27.19 CH 2 CH ₃ XIV CH O 27.20 CH 2 CH 2 CH ₃ XIV CH O 27.21 CH (CH ₃₎ from XIV CH O 27.22 CH 2 (CH 2) ₃ CHa XIV CH O 27.23 CH 2 (CH 2) 4 CHa XIV CH O 27.27 CH 2 CH (CH ₃ ) ₂ XIV CH O 27.25 CH (CHa) CH2 CHa XIV CH O 27.26 C (CH3) ₃ XIV CH O 27.27 CH 2 C (CHa) a XIV CH O 27. 28 CH (CHa) CH2 CH2 CH2 XIV CH O 27.29 C (CHa) ₂ CH2 CHa XIV CH O 27.30 CFa XIV CH 0 27.31 CF ₂ CF ₃ XIV CH O 27.32 CH 2 CF ₃ XIV CH O 27.33 CH = CH 2 XIV CH 0 27.34 cyclopropyl XIV CH O 27.35 cyclopentyl XIV CH 0 27.36 cyclohexyl XIV CH O 27.37 CH2OCH3 XIV CH O 27.38 CHz OCHz CHa XIV CH 0 27.39 CHz CHz OCOAr XIV CH 0 27.40 CHz OCHz Ar XIV CH O 27.41 2-pyridyl XIV CH O

• · ·

- 23 Table 27 - Completion

merge number (B) formula AND IN 27.42 3-pyridy1 XIV CH O 27.43 2-pyrimidyl XIV CH O 27.44 4-pyrimides1 XIV CH O 27.45 2-thienyl XIV CH O 27.46 3-thienyl XIV CH O 27.47 2-naphthyl1 XIV CH O 27.48 Ar XIV N 0 27.49 4 — Cl (Ar) XIV N O 27.50 ch ₃ XIV N O 27.51 CHz CHa XIV N O 27. 52 CHz CHz CHa XIV N O 27.53 CH 2 CH 2 _z XIV N O 27.54 CH 2 (CH 2) ₃ CH 3 XIV N 0 27. 55 Chichi CH) ₂ XIV N O 27.56 C (CH3) ₃ XIV N O 27.57 Ar XIV N NH 27.58 4 — Cl (Ar) XIV N NH 27.59 ch ₃ XIV N NH 27.60 CHz CHz CHa XIV N NH 27.61 CH (CH?) _Of XIV N NH 27.62 CH 2 (CH 2) ₃ CHa XIV N NH 27.63 CH 2 CH 2 CH 2) ₂ XIV N NH 27.64 C (CH3) ₃ XIV N NH 27.65 2-thienyl XIV N NH 27.66 3-thienyl XIV N NH 27.67 2-pyridyl XIV N NH 27.68 3-pyridy 1 XIV N NH 27.69 5 — pyrimidines1 XIV N NH 27.70 2-naphthyl XIV N NH

Typical compounds within the scope of the present invention of Formula I include those of Table 28 of the general formulas.

XVII, XVIII and XIX, wherein X = H, H 1 = H, U is N, W is O and n and m are 0.

R

(XVIII) (XVIII) (XIX)

Table 28

s1ouč. number R formula AND IN 28.01 Ar XVII CH O 28.02 Ar XVIII CH O 28.03 Ar XIX CH O 28. 04 4 — Cl (Ar) XVII CH 0 28.05 4 — Cl (Ar) XVIII CH O 28.06 4 — Cl (Ar) XIX CH O 28.07 4-F XVII CH O 28.08 4-F XVIII CH 0 28.09 4-F XIX CH O 28.10 2-CH 3 (Ar) XVII CH 0 28.11 2-CH (Ar) XVIII CH O 28.12 2-CHg (Ar) XIX CH 0 28.13 4-CH (Ar) XVII CH 0 28.14 4-CH (Ar) XVIII CH O 28.15 4-CH (Ar) XIX CH O

• · · · · ·

- 25 Table 28 - continued

merge number R formula AND IN 28.16 4-CF ₃ XIX CH O 28.17 2,4 — Cl (Ar) XIX CH 0 28.18 CHa XIX CH O 28.19 CHz CHa XIX CH O 28.20 CHz CHz CHa XIX CH O 28.21 CH (CHa) 2 XIX CH 0 28. 22 CH 2 (CH 2) ₃ CHa XIX CH 0 28.23 CH2 (CH2> 4CHa XIX CH O 28.27 CH 2 CH (CH ₃ ) ₂ XIX CH O 28.25 CH (CHa) CH2 CHa XIX CH O 28.26 C (CH3) ₃ XIX CH O 28.27 CH 2 C (CHa) a XIX CH O 28.28 CH (CHa) CH2 CH2 CH2 XIX CH O 28.29 C (CHa) 2 CH _from CHa XIX CH O 28.30 CFa XIX CH 0 28. 31 CFz CFa XIX CH 0 28.32 CH 2 CFa XIX CH O 28.33 CH = CH 2 XIX CH O 28. 34 cyclopropy1 XIX CH O 28.35 cyclopenty1 XIX CH O 28.36 cyclohexyl XIX CH O 28. 37 CHz OCHa XIX CH O 28.38 CHz OCHz CHa XIX CH O 28.39 CHz CHz OCOAr XIX CH 0 28.40 CHz OCHz Ar XIX CH O 28.41 2-pyridyl XIX CH O 28.42 3-pyridyl XIX CH 0 28.43 2-pyrimides1 XIX CH 0 28.44 4-pyrimides1 XIX CH O 28.45 2-thienyl XIX CH O 28.46 3-thienyl XIX CH O 28.47 2 — naítty1 XIX CH O

·· ····

- 26 Table 28 - Completion

s1ouč. number R formula AND IN 28.48 Ar XIX N O 28.49 4-Cl XIX N 0 28.50 CHa XIX N O 28.51 CHz CHa XIX N O 28. 52 CHz CHz CHa XIX N O 28. 53 CH (CHa) 2 XIX N O 28. 54 CH 2 (CH 2) ₃ CHa XIX N O 28.55 CH 2 CH (CH ₃ ) ₂ XIX N O 28.56 C (CH3) ₃ XIX N O 28.57 Ar XIX N NH 28.58 4 — Cl (Ar) XIX N NH 28.59 CHa XIX N NH 28. 60 CHz CHz CHa XIX N NH 28.61 CH (CH3) ₂ XIX N NH 28.62 CH 2 (CH 2) ₃ CHa XIX N NH 28.63 CH 2 CH (CH ₃ ) ₂ XIX N NH 28.64 C (CH ₃₎ and XIX N NH 28.65 2-thienyl XIX N NH 28.66 3-thienyl XIX N NH 28. 67 2-pyridyl XIX N NH 28.68 3-pyridy1 XIX N NH 28. 69 5 — pyrimidines1 XIX N NH 28.70 2-na1ty1 XIX N NH Typical compounds. falling into this invention,

H, U is O, W and N and m are 0.

of formula I, include the compounds of Table 29 of formulas XX, XXI and XXII, wherein X = H, R 1 = 9 · 9

(XX) (XXI)

Table 29

sloue. number Β formula AND IN 29.01 Ar XX CH 0 29.02 Ar XXI CH O 29.03 Ar XXII CH 0 29.04 4 — Cl (Ar) XX CH O 29. 05 4 — Cl (Ar) XXI CH O 29.06 4 — Cl (Ar) XXII CH O 29.07 4-F XX CH O 29.08 4-F XXI CH 0 29.09 4-F XXII CH O 29.10 2-CH (Ar) XX CH O 29.11 2-CH (Ar) XXI CH 0 29.12 2-CH (Ar) XXII CH O 29.13 4-CH 3 (Ar) XX CH 0 29.14 4-CH 3 (Ar) XXI CH O 29.15 4-CH 2 (Ar) XXII CH O 29.16 4-CFa (Ar) XX CH O

• · ·· »

- 28 Table 29 - continued

merge number R formula AND IN 29. 17 2.4 ~ Cl (Ar) XX CH O 29.18 CHs XX CH 0 29.19 CH 2 CH 2 XX CH O 29.20 CHz CHz CHa XX CH O 29.21 CH (CH3) ₂ XX CH O 29.22 CH 2 (CH 2) ₃ CH 3 XX CH O 29.23 CH 2 (CH 2) jCH 3 XX CH O 29. 27 CH 2 CH (CH 3) 2 XX CH O 29.25 CH 2 CH 2 CH 2 CH 3 XX CH O 29. 26 C (CH ₃ ) ₃ XX CH O 29.27 CH ₂ C (CH ₃ ) ₃ XX CH O 29.28 CH (CHa) CH2 CH2 CH2 XX CH O 29. 29 C (CH 2 is CH 2 CH 2 XX CH 0 29.30 cf ₃ XX CH O 29.31 CF ₂ CF ₃ XX CH O 29. 32 CH 2 CF ₃ XX CH O 29.33 CH = CH 2 XX CH O 29.34 cyclopropy1 XX CH O 29.35 cyclopentyl XX CH 0 29.36 cyclohexyl XX CH O 29. 37 CHz OCHa XX CH O 29.38 CH 2 OCH 2 CH ₃ XX CH O 29.39 CHz CHz OCOAr XX CH O 29.40 CHz OCHz Ar XX CH O 29.41 2-pyridyl XX CH O 29.42 3-pyridyl XX CH 0 29.43 2-pyrimidyl XX CH O 29.44 4-pyrimidyl XX CH O 29.45 2-thienyl XX CH O 29.46 3-thienyl XX CH 0 29.47 2-na1ty1 XX CH O 29.48 Ar XX N 0

··································

- 29 Table 29 - Completion

s1ouč. number R formula AND IN 29.49 4 — Cl (Ar) XX N O 29.50 CHa XX N 0 29.51 CHz CHa XX N 0 29.52 CHz CHz CHa XX N O 29.53 CH (CHa) 2 XX N O 29.54 CH 2 (CH 2) ₃ CHa XX N O 29.55 CH 2 CH (CH ₃ ) ₂ XX N 0 29.56 C (CH3) a XX N O 29.57 Ar XX N NH 29.58 4 — Cl (Ar) XX N NH 29.59 CHa XX N NH 29.60 CHz CHz CHa XX N NH 29.61 CH (CH3) ₂ XX N NH 29.62 CH2 (CH2) and CH2 XX N NH 29.63 CH 2 CH (CH 3) 2 XX N NH 29.64 C (CH3) ₃ XX N NH 29.65 2-thienyl XX N NH 29.66 3-thienyl XX N NH 29. 67 2-pyridyl XX N NH 29.68 3-pyridy 1 XX N NH 29. 69 5 — pyrimidines1 XX N NH 29.70 2-na1ty1 XX N NH

Typical compounds of this invention of Formula I include those of Table 30 of Formulas XXIII, XXIV, and XXV, wherein X = H, R 1 = H, U is N, W is O, and n is 0.

• · · ·

- 30 R

(XXV) (XXIV) (XXIV)

Table 30

s1ouč. number R formula AND IN 30.01 Ar XXIII CH O 30.02 Ar XXIV CH O 30.03 Ar- XXV CH O 30.04 4 — Cl (Ar) XXIII CH O 30.05 4-Cl XXIV CH 0 30.06 4 — Cl (Ar) XXV CH 0 30.07 4-F XXIII CH O 30.08 4-F XXIV CH O 30.09 4-F XXV CH O 30.10 2-CH (Ar) XXIII CH O Nov 30 2-CH (Ar) XXIV CH O 30.12 2 — CHa (Ar) XXV CH O 30.13 4-CH (Ar) XXIII CH O 30.14 4 — CHa (Ar) XXIV CH 0 30.15 4-CH (Ar) XXV CH O 30.16 4-CFa (Ar) XXIII CH 0 30.17 2,4 — Cl (Ar) XXIII CH O 30. 18 CHa XXIII CH O

·· ·

AND

- 31 Table 30 - continued

merge number R formula AND IN 30.19 CH _Z CHs XXIII CH O 30.20 CH 2 CH 2 CH ₃ XXIII CH 0 30.21 CH ₂ CH ₂ ) XXIII CH O 30.22 CH 2 (CH 2) and CH ₃ XXIII CH O 30. 23 CH 2 (CH 2) 4 0¾ XXIII CH O 30. 27 CH ₂ CH ₂ CH ₂ XXIII CH O 30.25 CH (CH ₃ JCH ₂ CH ₃ XXIII CH O 30.26 C (CH3) ₃ XXIII CH O 30.27 CH2 (CH2CH3) ₃ XXIII CH O 30. 28 CH (CH ₃ ) CH _from CH 2 CH 8 XXIII CH O 30. 30 C (CH 2 J 2 CH 2 CH 3 XXIII CH O 30.30 cf ₃ XXIII CH O 30.31 CF ₂ CF ₃ XXIII CH O 30.32 CH 2 CF ₃ XXIII CH O 30. 33 CH = CH 2 XXIII CH O 30. 34 cyclopropy1 XXIII CH O 30.35 cyclopenty1 XXIII CH O 30.36 cyclohexyl XXIII CH O 30. 37 CHz OCHs XXIII CH 0 30. 38 CHz OCHz CHs XXIII CH O 30. 39 CHz CHz OCOAr XXIII CH O 30.40 CHz OCHz Ar XXIII CH O 30.41 2-pyridyl XXIII CH O 30.42 3-pyridyl XXIII CH O 30.43 2-pyrimidyl XXIII CH O 30.44 4-pyrimidyl XXIII CH O 30.45 2-thienyl XXIII CH 0 30.46 3-thienyl XXIII CH O 30.47 2-naphthyl1 XXIII CH O 30.48 Ar XXIII N 0 30.49 4 — Cl (Ar) XXIII N O 30.50 ch ₃ XXIII N O

• · · ·

- 32 Table 30 - Completion

merge number R formula AND IN 30.51 CH 2 CH 3 XXIII N O 30.52 CHz CHz CHa XXIII N O 30.53 CH (CH3) ₂ XXIII N O 30.54 CH 2 (CH 2) ₃ CH ₃ XXIII N O 30.55 CH ₂ CH (CH ₃ ) ₂ XXIII N O 30.56 CÍCHa) ₃ XXIII N O 30.57 Ar XXIII N NH 30.58 4 — Cl (Ar) XXIII N NH 30.59 CHa XXIII N NH 30. 60 CHz CHz CHa XXIII N NH 30.61 CH (CHa) 2 XXIII N NH 30.62 CH 2 (CH 2) ₃ CHa XXIII N NH 30. 63 CH 2 CH (CH ₃ ) 2 XXIII N NH 30.64 C (CH3) ₃ XXIII N NH 30. 65 2-thienyl XXIII N NH 30. 66 3-thienyl XXIII N NH 30.67 2 — pyridy1 XXIII N NH 30. 68 3-pyridy1 XXIII N NH 30.69 5-pyrimidynyl XXIII N NH 30.70 2-Naphthyl XXIII N NH Symbol Ar in Tables 1 to 30 poses females 1

The compounds of formula (I) are prepared in successive steps. Schemes A and B describe the preparation of compounds of formula I, wherein η = 1 and m = 0 of, (3 unsaturated compound of formula XXVI is prepared by conventional condensation techniques. For example Organic Reactions Publication ^_ Organic Reactions, Volume 16 describes the general aldol condensation and specifically the condensation of benzaldehyde ₍ R) with ketones.

• · · ·

When R 1 = H is methyl ketone, it gives the unsaturated intermediate of formula XXVI.

Hydroxybenzaldehyde such as ortho, meta or parahydroxy-benzaldehyde gives the three regioisomeric intermediates XXVI and XXVI. By varying the reaction conditions, compounds XXVI and XXVI are prepared as described in Organic Beactions, Volume 16, pp. 69-85. For example, the ketone is dissolved in a solvent with hydroxyl groups such as ethanol to which a solution of hydroxybenzaldehyde in an aqueous basic solution is added dropwise. The base used may be an alkali metal hydroxide such as potassium or sodium hydroxide and the dropwise addition is carried out at temperatures from 0 ° C to 35 ° C, preferably at room temperature.

The intermediate of formula XXVI is reacted with hydrazine or substituted hydrazine to give the intermediate of pyrazolines of formula XXVII. A typical preparation of pyrosoline from unsaturated enones by hydrazine treatment (for Z = H) is described in Synthetic Commun, 25 (12), 1877-1883 (1995); JACS 73, 3840 (1951); Indian Chem Chem Soc B 98-104 (1992) and Chem Chem Chem 643-644 (1993). For example, in JACS 73, 3840 (1951), styrylcyclopropyl ketone is reacted with aqueous hydrazine in 95% ethanol and stirred on a steam bath for one hour, yielding a pyrazoline yield of 86% after distillation. Similarly, in Synthetic Commun, 25 (12), 1877-1883 (1995), chalcones are reacted with hydrazine monohydrate under stirring and refluxing in ethanol to yield pyrazolines greater than 90% by weight.

A typical preparation of N-pyrazolo [beta] 1 (when Z is phenyl) from unsaturated ones is described in Indian J. Chem Soc Sec B 98-104 (1992), J. Chem Res. Synop. 5, 168-169 (1994) and Bull Soc. Chim Belg. 707 (1958). For example, in J. Chem Res. Synop. 5,

168-169 (1994) reacts chalcone with excess phenylhydrazine under reflux in ethanol to give N-phenylpyrazolines in yield

60-70% by weight. Similarly, in Indian J. Chem Soc Séct

B 98-104 (1992) gave N-phenylpyrazoline in 88% yield reaction of unsaturated carbonyl compound

with 1 hydrazine under reflux in the presence of glacial acetic acid.

The isoxazoline intermediates of formula XXVIII are prepared from an enone of formula XXVI by reaction with hydroxylamine as described in Bull Soc. Chim Belgr 96 (4), 293 (1987) and in Collect Czech Chem. Commun. 59: 247-252 (1994). Typically, the enone is treated with an equimolar amount of hydroxylamine hydrochloride in 0.3 M ethanolic sodium hydroxide and stirred under reflux for up to 10 hours and after neutralization with HCl the product is isolated by filtration.

Preparation of the pyrazole of general formula XXIX '· ζ. the intermediate pyrazoline of formula XXVII is described in J. Indian Chem Soc. 64 (7), 408 (1987) by oxidation of MnO 2 at room temperature. Typically, the pyrazolines are shaken with 3.0 equivalents of MnO 2 in chloroform at room temperature for 2 hours and the pyrazoles are isolated by chromatography.

The preparation of isoxazoles of formula XXX from the isoxazoline intermediate of formula XXVIII is described in Synthesis 837 (1997) and Synth. Commun. 219 (1978). Typically, the 3,5-di-substituted-isoxazoline in a 10: 1 benzene: dioxane mixture is treated with gamma MnO 2 (5.0 equivalents by weight) and stirred under reflux with azeotropic water removal using a Dean Stark trap. The reaction mixture was filtered through celite and the remaining residue contained isoxazole.

- 35 Scheme A:

^R.

when R 1 = H

R (XXVI ’)

H

O

R— + CH,

(XXVI ’)

OH

Compounds of Formulas V, VI, VII; XVII, XVIII, XIX; XI, XII, XIII and XXIII, XXIV, XXXV are prepared by alkalizing the pyrazoline intermediate of formula XXVII (when Z is not,) and the isoxazoles of general formula XXVIII and pyrazole of formula XXIX (when Z is not H) and isoxazole XXX, respectively, respectively bezylbromides as depicted in Scheme B.

If Z is H, then intermediates of general formulas XXVII

XXIX is alkylated with Z-L, wherein L is halogen and formed

The -36 O, N-dialkylated products are selectively O-dialkylated with HBr to give intermediates of formulas XXVII and XXIX, wherein Z is not H.

Alkylation of the pyrazole intermediate of formula XXVII, derived from meta-hydroxybenzaldehyde, gives compounds of Tables 11-20 of formula V (where R 1 = H). Alkylation of the intermediate of formula XXVII, derived from orthohydroxybenzaldehyde, provides compounds of Tables 11-20 of Formula VI (where R 1 = H). Alkylation of the intermediate of formula XXVII, derived from para-hydroxybenzaldehyde, provides compounds of Tables 11-20 of Formula VII (where R 1 = H). Alkylation of the isoxazoline intermediate of formula XXVIII, derived from meta-hydroxybenzaldehyde, gives the compounds of Table 28 of formula XVII (where R 1 = H). Alkylation of an intermediate of formula XXVIII, derived from orthohydroxybenzaldehyde, provides compounds of Table 28 of formula XVIII (where R 1 = H). Alkylation of the intermediate of formula XXVIII, derived from para-hydroxybenzaldehyde, provides compounds of Table 28 of formula XVIII (where R 1 = H).

Alkylation of the pyrazole intermediate of formula XXIX, z

derived from a pyrazoline of formula XXVII gives compounds of Tables 24 to 26 of formulas XI, XII and XIII (where R 1 = H). Alkylation of the isoxal intermediate of formula XXX, derived from the isoxazoline of formula XXVIII, gives compounds of Table 30 of formulas XXIII, XXIV and XXV (where R 1 = H).

Compounds of formula I wherein A is CH and V is O is prepared by alkylating methyl 1-E-c- (2-bromomethylphenyl) -O-methoxyacrylate in the presence of a base such as a metal hydride, preferably NaH, in an aprotic solvent such as N, N- dimethylformamide. Methyl E-α- (2-bromomethylphenylene) -O-methoxy acrylate, as the sole isomer E, was prepared in two steps from 2-methylienylacetate, as previously described in U.S. Patent No. 4,914,128, columns 3-4 .

• · • ·

Compounds of formula VI wherein A is N and V is oxygen is prepared by reacting methyl-E- 2- (bromomethyl) phenylglyoxylate-O-methyloxime in the presence of a base such as a metal hydride, preferably NaH, in an aprotic solvent such as N, N-dimethylformamide. Methyl 2- (bromomethyl) phenylglyoxylate-O-methyloxime is prepared as described in U.S. Patent Nos. 4,999,042, col. 17-18 and 5,157,144, pp. 17-18. Methyl 2- (bromomethyl) phenylglyoxylate-O-methyl-oxime is prepared from methyl-2-methylphenylacetate by treatment with alkylditanium under basic conditions to give methyl-2-methylphenylglyoxylate-O-methyloxime after methylation, which can also be prepared from 2 —Methylphenylglyoxalate by reaction with 2-hydroxylamine hydrochloride and methylation or by reaction with methoxylamine hydrochloride.

An alternative synthetic route to the examples, when A is N and V is oxygen, is provided by reacting V A (V) with methyl 2- (bromomethyl) phenylglyoxalate, followed by reaction with methoxy oxylamine or hydroxylamine hydrochloride followed by methylation.

Ammonolysis of oximinoacetate to oximinoacetamides is described in U.S. Patent Nos. 5,185,342, col. 22, 48 and 57; 5,221,691, col. 26-27 and 5,407,902, col. 8. Compounds of formula VI wherein A is N and V is O are treated with 40% aqueous methylamine in methanol to give compounds of formula V wherein V is NH (CH 3). The compound of formula V and V is reacted with N-methyl-E-2-methoxyimino-2- [2-bromoethyl) phenyl] acetamide in the presence of a base such as a metal hydride, preferably NaH, in an aprotic solvent such as dimethylformamide (DMF).

N-methyl-E-2-methoxyimino-2- [2- (bromomethyl) phenyl] acetamide is described in US Patent No. 5,387,714, col. 13.

• ·

- 38 Scheme Β:

V, VI, VII; XI, XII, XIII

XXV)

Scheme C describes a process for the preparation of compounds of formula I wherein n = 0 and m = 1.?, (3 unsaturated compounds of formula XXXI are prepared by a conventional condensation method).

For example, Organic Reaction, Volume 16 describes general aldol condensation and specifically condensation of aldehydes with ketones. The aldehyde, e.g., substituted benzaldehyde, is condensed with hydroxyphenyl ketone, (OH) ArCOCl 2 Bi, which, when Bi = H is methyl ketone, gives the unsaturated intermediate of formula XXXI.

• · · · · ·

- 39 Scheme C:

O

R - + H (XXXI)

OH / R.

OH where R 1 = H (XXXI ¹ ) i _H

(XXXV)

Substituted hydroxyphenyl ketones such as ortho, meta or para-hydroxyacetophenone provide three regioisomeric intermediates

XXXI, where R 1 = X = H. The intermediate enone XXXI reacts with hydrazine, substituted hydrazines and hydroxylamine in the same manner as intermediate XXVI (Scheme A). The pyrazoles XXIV 'and the isoxazoles XXXV' are prepared by oxidation of the pyrazoline _of general formula

XXXII and isoxazoline XXXIII, respectively, in the same manner as described in Scheme A.

• ·

- 40 Compounds of formulas II, III, IV; VIII, IX, X; XIV, XV, XVI and XX, XXI, XXII are prepared by alkylation of the intermediate ppyrazoline XXXII and isoxazolines XXXIII and pyrazole XXIV and XXXV respectively with the corresponding substituted benzyl bromides as described in Scheme D.

Alkylation of the pyrazoline intermediate XXXII, derived from meta-hydroxyacetophenone, yields compounds of Tables 1 to 10 of formula II (where R 1 = H). Alkylation of the isoxazoline intermediate of formula (XXXII ') derived from orthoacetoenenone gives compounds of Tables 1 to 10 of formula (III) (where R 1 = H). Alkylation of the intermediate of formula (XXXII) derived from para-hydroxyacetophenone gives compounds of Tables 1 to 10 of formula (IV) (wherein R 1 = H). Alkylation of the intermediate of formula XXXIII, derived from metahydroxyacetophenone, gives the compounds of Table 27 of formula XIV (where R 1 = H). Alkylation of the intermediate of formula XXXIII, derived from ortho-hydroxyacetophenone, yields compounds of Table 27 of formula XV (where R 1 = H). Alkylation of the intermediate of formula XXXIII, derived from parahydroxyacetophenone, gives the compounds of Table 27 of formula XVI (where R 1 = H).

Alkylation of the pyrazoline intermediate XXXIV, derived from the pyrazoline of formula XXXII, gives compounds of Tables 21 to 23 of formulas VIII, IX and X (where R 1 = H). Alkylation of the isoxazoline intermediate of formula XXXV, derived from the isoxazoline of formula XXXIII, gives compounds of Table 29 of formulas XX, XXI and XXII (where R 1 = H).

·· ····

Br

CO (V) CH ₃ h ₃ co

-

(ΧΧΧΠΓ, XXXV ’)

The compounds of the invention can be prepared according to the following procedures:

DETAILED DESCRIPTION OF THE INVENTION

Example 1

Methyl-3-methoxy-2- [2- (3- (1-methyl-5-phenyl-2-pyrazolin-3-yl) -phenoxymethyl) -phenyl) propenoate (Compound 1.01, Table 1)

In a 25 ml vial equipped with a magnetic stir bar, 1.1 g (0.0045 mol) of 3- (3-hydroxyphenyl) -1-methyl-5-phenyl-2-pyrazoline and 0.3 g (0, [0045] 85% by weight of pulverulent potassium hydroxide and 15 ml of dry N, N-dimethylformamide. To this solution was added 1/3 g (0.0045 mol) of d- (2- (bromomethyl) phenyl) -O-methoxyacrylate. The vial was sealed and the reaction mixture was stirred overnight at room temperature. The reaction mixture was then poured into 100 ml of water and extracted with 2x100 ml of ethyl acetate. The organic extract was

X is then washed with 100 ml of water and 100 ml of saturated aqueous sodium chloride solution. Then, the organic extract is dried over anhydrous magnesium sulfate and then filtered. The filtrate is concentrated under reduced pressure and the residue is chromatographed on a mixed bed of neutral alumina and silica gel with 50% ethyl acetate and 50 35 hexane. The pure fractions were combined and concentrated under reduced pressure to give 1.9 g (92% yield) of methyl 3-methoxy-2- [2- (3- (1-methyl-5-phenyl) -2-pyrazolin-3-yl)]. (phenoxymethyl) phenyl] propenoate as an amber oil.

1 H-NMR (200 MHz, CDCl 3): 2.9 (s, 3H); 3.5 (m. 2H); 3.7 (s. 3H); 3.9 (s. 3H); 4.1 (m, 1H); 5.0 (s. 2H); 6.9 (m, 1H); 7.1-1.5 (m,

12H); 7.6 (s, 1H);

Preparation of 3- (3-hydroxyphenyl) -1-methyl-5-phenyl-2-pyrazoline from 3-hydroxychalcone

In a 100 ml round bottom flask equipped with a magnetic stirrer and a reflux condenser was charged 1.0 g (0.0045 mol) of 3-hydroxychalcone and 25 ml of absolute ethanol. To this solution was added 0.21 g (0.0045 mol) of methylhydrazine in one portion. The reaction mixture was then heated at reflux temperature for 2 hours and then cooled. The solvent was removed under reduced pressure to give 1.1 g of 3- (3-hydroxyphenyl) -1-methyl-5-phenyl-12-pyrazoline as a thick brown oil in 97% yield.

1 H-NMR 200MHz (CDCl 3): 2.9 (s, 3H); 3.0 (t, 1H); 3.4 (dd, 1H);

4.2 (dd, 1H); 6.8-7.6 (m. 9H); 11.0 (br s, 1H).

• 9,999 • ·

- 43 Example 2

Methyl-3-methoxy-2- [2- (3- (1-methyl-3-phenyl-2-pyrazolin-5-yl) phenoxymethyl) phenyl] propenoate (Compound 11.01, Table 11).

To a 25 ml ampoule equipped with a magnetic stir bar was added 1.1 g (0.0045 mol) of 5- (3-hydroxyphenyl) -1-methyl-3-phenyl-2-pyrazoline, 0.3 g (0.0045 mol) of powdered potassium hydroxide (85% by weight) and 15 ml of dry N, N-dimethylformamide. To this solution was added 1.3 g (0.0045 mol) of N - (2-bromoethyl) phenyl) - (3-methoxy acrylate) and the vial was sealed and stirred at room temperature overnight. The organic extract was then washed with water (2.times.100 ml) and saturated aqueous sodium chloride (100 ml) and the organic extract was dried over anhydrous magnesium sulphate and then filtered. It is concentrated under reduced pressure and the residue is chromatographed on a mixed bed of neutral alumina and silica gel, eluting with 50% ethyl acetate, 50% hexane, and the pure fractions are combined and concentrated under reduced pressure to give 1.8 g of methyl-3-methoxy-2- [2- (3- (1-methyl-3-phenyl-2-pyrazolin-5-yl) phenoxymethyl) phenyl] propenoate as an amber oil in 88% yield.

1 H-NMR (200 MHz, CDCl ₃ ): 2.8 (s, 3H); 3.0 (t, 1H); 3.5 (m, 1H); 3.7 (s, 3H); 3.9 (s. 3H); 4.1 (m, 1H); 5.0 (s. 2H); 6.8 (d, 1H);

6.9 (d, 1H); 7.1-7.8 (m, 12H);

Preparation of 5- (3-hydroxyphenyl) -1-methyl-3-phenyl-2-pyrazoline from 3-hydroxychalcone

In a 100 ml round bottom flask equipped with a magnetic stirrer and a reflux condenser was charged 1.0 g (0.0045 mol) of 3-hydroxychalcone and 25 ml of absolute ethanol. To this solution was added 0.21 g (0.0045 mol) of methylhydrazine in one portion. The reaction mixture was then heated to reflux for 2 hours.

- 44 temperature and then cooled. The solvent was removed under reduced pressure to give 1.1 g of 5- (3-hydroxyphenyl) -1-methyl-3-phenyl-12-pyrazoline as a thick brown oil in 97% yield.

1 H-NMR 200MHz (CDCl 3): 2.9 (s, 3H); 3.0 (t, 1 H); 3.4 (dd, IH); 4.2 (dd, IH); 6.8-7.6 (m. 9H); 11.0 (bs, 1H).

Example 3

Table 31 provides proton nuclear resonance (1 H-NMR) (200 MHz) data for the compounds of Tables 1 to 12 and is illustrative of the invention.

Table 31

č.slouč.

1.01 2.9 (s. 3H); 3.5 (m. 2H); 3.7 (s. 3H); 3.9 (s. 3H); 4.1 (m. 1H); 5.0 (s. 2H); 6.9 (m, 1H); 7,1-7, Δ (m, 12H); 7 , 6 (s, 1H); 1.02 2.85 (s, 3H); 3.3 (m, IH) ; 3.5 (m, IH) ; 3.7 (s. 3H) ; 3.9 (s 3H); 4.1 (m, 1H); 5.0 (s, 2H); 6.8 (d, 1H); 6.9 (t, 1H), 7.2-7.5 (m. 10H); 7.6 (s, 1H); 7.8 (d, 1H) 1.03 2.8 (s. 3H); 3.0 (t, 1 H); 3.5 (m, 1 H); 3.7 (s. 3H) 3.9 (s. 3H); 4.1 (m, 1H); 5.0 (s. 2H); 6.8 (d, 1 H); 7,1 l (m. 1H); 7.2 - 7.7 (m, 12H) 1.57 3.2 (m, 1 H); 3.7 (s. 3H); 3.9 (s. 3H); 4, Km, 1H); 5.0 (s, 2H); 5.2 (m. 1H); 6.8 (d, 1H); 7,2-7, Δ (m, 15H); 7 , 7 (s, 1H); 8.0 (m, IH) 11.01 2.8 (s. 3H); 3.0 (t, 1 H); 3.5 (m, 1 H); 3.7 (s. 3H); 3.9 (s, 3H); 4.1 (m, 1H); 5.0 (s, 2H); 6.8 (d, 1H); 6.9 (d, 1H); 7.1 - 7.8 (m, 12H) 11.02 2.8 (m, 1H); 2.9 (s, 3H); 3.6 (m, IH); 3.7 (s. 3H); 3.9 (s, 3H); 4.5 (m, 1 H); 5.0 (s, 2H); 6.8 (d, 1H); 6.9 (t, 1H); 7.1-7.5 (m, 7H); 7.6 (m, 1H); 7.7 (m, 4H)

r · · · *

• · · · · · · · · · ·

Table 31 - continued

č.slouč.

··· · • ·

Example 4

Numerous compounds of this invention have been tested for fungicidal activity in vivo against the diseases described below. Compounds were dissolved in 2: 1: 1 (parts by weight) water, acetone and methanol, sprayed on the plants, allowed to dry (one to two hours), and then the plants were infected with fungi. Control plants were used in each test, which were sprayed with a mixture of water, acetone and methanol and infected with a fungus. The remaining procedure of each test and the results for the various compounds described herein by the example numbers in Table 4 against different fungi at a dose of 300 µg per hectare are given below. The results are reported as a percentage of the efficacy of the composition relative to the control sample, with one hundred calculated as the full efficacy of the composition and zero being ineffective. The application of fungi to the test plants was as follows:

Foam Rust (Wheat Leave Growth - WLR)

Puccinia recondita (i. Sp. Tritici) was cultured on 7 days old wheat (cultivar Fielder) for 14 days in a greenhouse. The spores were collected from the leaves by settling on aluminum foil. The spores were cleaned by sieving on a 250 micron sieve and stored or used fresh.

* · ·· ·· ·

The sealed bags were stored in an ultra low temperature freezer. The spore suspension was prepared from dry matter by adding 20 mg (9.5 million spores) per ml of Soltrol oil. The suspension was dispensed into gelatin capsules (volume 0.1 ml) which was mounted in oil sprayers. One capsule is used for a total area of twenty containers, each with an area of 12.9 cm ² (2 square inches) with 7 day Fielder wheat. After waiting for at least 15 minutes to evaporate the oil from the leaves, the plants were placed in a dark cloud chamber (18-20 ° C and 100% relative humidity) for 24 hours. The plants were then transferred to the greenhouse for a latent period and the extent of the disease was evaluated after 10 days. For protection tests, plants are infected one day after spraying the plants with fungicidal compounds.

Wheat Leaves (Wheat Leaí Blotch - SNW)

Septoria nodorum was maintained on Czapek-Dox V-8 agar plates in an incubator in the dark at 20 ° C for 48-72 hours, then incubated at 20 ° C with alternating 12 hours of light and 12 hours of darkness. The aqueous spore suspension was obtained by shaking a portion of the plate with the fungal material in deionized water and filtering through a filter cloth. The spores containing the aqueous suspension were diluted to a concentration of 3.0x10 6 spores per ml. The inoculum was dispersed with a DeVilbiss sprayer for one week old Fielder wheat plants that had previously been sprayed with the fungicidal compound. The infected plants were placed in a humid chamber at 20 ° C for 96 hours alternating with 12 hours of light and 12 hours of darkness. The infected seed was then transferred to a controlled room at 20 ° C for 8 days for incubation. The values of the extent of the disease found were recorded as a percentage of the efficacy of the composition.

• · · · ·

I · · »·

- 47 Wheat Powdery Mildew (WPM)

Erysiphe graminis (i. Sp. Tritici) was cultivated on wheat seedlings at a controlled room temperature of 18.33 ° C to 21.1 ° C (65 ° F to 70 ° F). The gangrene spores were shaken from the cultivated plants onto wheat seed which had been sprayed with a fungicidal compound. The infected seed was kept at a controlled room temperature at 18.33 ° C to 21.1 ° C (65 ° F to 70 ° F) and underwater irrigation. The percent efficacy of the composition was determined 8-10 days after infection.

Cucumber Powdery Mildew (CPM)

Sphaerotheca ilulginea was fed in the greenhouse on cucumber plants of the Bush Champion variety. The inoculum was prepared by washing the leaf spores with water in which 1 drop of Tween 80 and 100 ml was present. After shaking the plants, the inoculum was filtered through a filter cloth and sprayed onto the plants from the sprayer. The plants were then transferred to a greenhouse for infection and incubation. The extent of infestation was determined eight days after infection. Disease range values were recorded as a percentage of the efficacy of the composition.

Tomato Mold Blight (TLB)

Phytophthora inestans was cultured on V8 juice plus CaCO 3 agar for three to four weeks. The spores were washed from agar with water and dispersed with a DeVilbiss sprayer onto the leaves of three week old Pixie tomato plants that had been sprayed with experimental fungicides. The infected plants were placed in a humid chamber at 20 ° C for 24 hours for infection. The plants were then transferred to a room with a controlled environment at 20 ° C. The extent of disease was measured on plants after five days.

Grape Downy Mildew (GDM)

Plasmopara vticola was cultivated on leaves of live vine plants, Delaware variety, in a temperature-controlled chamber at 20 ° C in humid air with moderate light intensity for 7 to 8 days. An aqueous spore suspension of infested leaves was obtained and the spore concentration was adjusted to 3x10 @ 10 per ml of water. Delaware plants were infected by spraying on the underside of the leaves with a DeVilbiss sprayer until small drops on the leaves were noticeable. The infected plants were incubated in a cloud chamber for 24 hours at 20 ° C. The disease extent values were recorded as a percentage of the efficacy of the composition seven days after the injection.

When tested for resistance to sphaerotheca ilginea (CPM) at a dose of 300 grams per hectare, Examples 1.02, 11.02, 12.01, 14.01 showed an efficacy of 90% or better.

When tested for resistance to septoria nodorum (SNW) at a dose of 300 grams per hectare, Examples 1.02, 11.01, 12.01, 14.01 showed an efficiency of 90% or better.

In the Puccinia Recondita (WLR) resistance test at a dose of 300 grams per hectare, Examples 1.01, 1.02, 11.01, 11.02, 12.01, 14.01 showed an efficacy of 90% or better.

When tested against erysiphe graminis (WPM) at a dose of 300 grams per hectare, Examples 1.01, 1.02, 12.01 showed an efficacy of 75% or better.

When tested for resistance to plasmopara vticola (GDM) also at a dose of 300 grams per hectare, Examples 1.01, 1.02, 11.01, 11.02, 12.01, 14.01 showed an efficacy of 95% or better.

The compounds of the present invention are useful as agricultural fungicides and as such may be of various application as seed, soil or leaf protection.

The compounds of the present invention can be applied as fungicidal sprays by conventional methods such as conventional large-volume liquid sprays, small-scale sprays, air-sprayed sprays, airborne sprays, and powders. The dilutions and application rates will depend on the type of device used, the mode of application, the plant being treated and the disease to be controlled. In general, the compounds according to the invention are applied in a ratio of from 0.005 kg to 50 kg per hectare and preferably from 0.025 to 25 kg per hectare, based on the active ingredient.

As seed protection agent, the amount of poison in the seed coating is generally in doses of 0.05 to 20 g, preferably 0.05 to 4 g, and more preferably 0.1 to 1 g per 100 kilograms of seed. As a soil fungicide, the chemical may be incorporated into the soil, or it may be applied to the surface generally at doses of from 0.02 to 20 kg, preferably from 0.05 to 10 kg, and more preferably from 0.1 to 5 kg per hectare. As foliar fungicide, the poison is usually applied to growing plants at doses of from 0.01 to 10 kg, preferably from 0.02 to 5 kg, and even more preferably from 0.25 to 1 kg per hectare.

Since the compounds of the present invention exhibit fungicidal activity, these compounds may be combined with other known fungicides to achieve a broad spectrum of activity. Suitable fungicides include, but are not limited to, the compounds listed in U.S. Pat. No. 5,252,594 (see especially columns 14 and 15).

The compounds of the invention may be advantageously used in various ways. Since these compounds have a broad spectrum of fungicidal activity, they can be used in the storage of cereal grains. These complexes can also be used as fungicides.

- 50 for cereals, including wheat, barley and rye, rice, peanuts, beans and grapes, on lawns, in fruit, nut and vegetable gardens and on golf courses.

Examples of diseases against which the compounds of the invention are useful include corn and barley helminthosporium, powdery mildew on wheat and barley, wheat rust on leaves and stem, early and late blight on tomatoes, early blight of peanuts, vine blight, black rot vine, apple scab, apple powdery mildew, cucumber powdery mildew, brown rot of fruit, botrytis, bean powdery mildew, cucumber anthracnosa, wheatgrass, rice mold and rice plague.

Example 5

Numerous compounds of this invention have been tested for insecticidal activity in vivo against insects as described below. The following test method was used to evaluate the compounds of this invention for insecticidal activity. The compound to be tested was dissolved in an appropriate solvent, usually a mixture of acetone, methanol and water, and sprayed with a flat fan nozzle onto three excited leaf blades. After spraying, the leaf blades were allowed to dry. Two blades were infested with leaf-eating insects (southern warrior and herbivorous ladybird) and the third leaf blade was already infested with the mite. The insect species tested were:

AW Southern soldier Spodoptera eridamia BB ladybird Epilachna varivestis MTA mite Teranychus uricate Visually found builds 24-48 hours after spraying was

as a percentage of efficiency.

When tested for Spodoptera eridamia at 600 g / ha, Examples 1.43 and 7.10 provide 90% or better mastery.

51 When tested for Epilachna varivestis at 300 g / ha Examples 1.07, 1.10, 1.18, 1.21, 1.27, 1.38, 1.39, 1.41, 1.43, 1.65, 2.03 and 7.10 provide 90% or better mastery.

When tested for Teranychus uricate at 300 g / ha, Examples 1.38 and 2.03 provide 90% or better mastering.

The compositions and compounds of the invention are applicable directly to the site to be protected, such as the area around or to plants infested with insects or plants to be prevented from infestation. Examples of harmful insects include the order Lepidoptera, Coleoptera,

Diptera, Thysanoptera, Hymenoptera, Heteroptera, Homoptera, Orthoptera, and Acarina. The compounds and compositions are used either as contact or systemic pesticides. The compounds according to the invention are applied to insect occurrence at doses of 0.0005 to 10 kg per hectare, preferably 0.05 to 5 kg / ha and even more preferably from 0.1 to 1 kg / ha.

In practice, according to the invention, the active compound is applied to the soil or leaves where it is absorbed by the plant, transferred to other parts of the plant and finally absorbed by pests or insects through the absorption of part (s) of the plant. This method of application is understood as systemic application. Alternatively, the active compound can be applied to the soil and contacted therein, i.e., contacting insects or other pests to be controlled. This method of application is called soil application. In another alternative, the active compound is applied foliarly to a plant to be free of insects or other foliage pests.

The compositions and formulations of the invention may also contain known pesticidal compounds. This broadens the spectrum of activity of the composition. Known suitable insecticides known in the art include the insecticides listed in U.S. Pat. patent

5,075,471, see in particular columns 14 and 15.

·· ·· * ·

The compounds of this invention are used in a variety of compositions and formulations. Examples of formulation preparations and formulations can be found in Pesticidal Chemical Research - Research of Pesticide Formulations of the American Chemical Society, Advances in Chemistry Series No. 86 by Wade Van Valkenburg and in Marcel Dekker, Inc. Pesticide Formulations, (1973), edited by Wade Van Valkenburg. In these compositions and formulations, the active compound is admixed with conventional inert agriculturally acceptable (i.e., plant compatible and / or pesticidally inert) pesticidal diluents or extenders such as solid carrier materials or liquid carrier materials of the type useful in conventional pesticidal compositions and formulations. By agriculturally acceptable carrier is meant any substance that can be used to dissolve, disperse the active ingredient in the composition without adversely affecting the effectiveness of the ingredients and which in itself has no significant deleterious effect on the soil, plant, desired plant or agricultural environment. If desired, additives such as surfactants, stabilizers, antifoams and antidrift agents can be combined.

Examples of compositions and formulations of the present invention are aqueous solutions and dispersions, oil solutions and oil dispersions, pastes, spray powders, wettable powders, emulsifiable concentrates, liquid formulations, granules, baits, inverse emulsions, aerosol formulations and fumed candles. Wettable powders, pastes, liquid compositions, and emulsifiable concentrates are concentrated formulations that are diluted with water before or during use. In such formulations, the compounds are adjusted with a liquid or solid carrier, and if desired, a suitable surfactant is incorporated. Baits are formulations generally comprising a food or other substance that is attractive to insects, comprising at least one compound of the invention.

• ·

It is generally desirable, particularly in the case of leaf spray formulations, to incorporate ingredients such as wetting agents, wetting agents, dispersing agents, adhesives, adhesives and the like, in accordance with agrotechnical practice. Such additives are generally used in the art, and discussions of these can be found in a number of references, for example, in John W. McCutcheon et al., Detergents and Emulsiíiers, Annual Detergents and Emulsifiers.

The active compounds according to the invention are used alone or in the form of mixtures with another compound and / or with such solid and / or liquid dispersing carriers and / or other known compatible active agents, in particular plant protection agents such as other insecticides, arthropodicides, nematicides , fungicides, bactericides, rodenticides, herbicides, fertilizers, growth regulators and synergists.

In the compositions of the invention, the active compound is present in an amount substantially between 0.0001 to 99% by weight. For compositions suitable for storage or transport, the amount of active ingredient is preferably between 0.5 and 90% by weight and even more preferably between 1 and 75% by weight of the composition. Compositions suitable for direct application or for field application have an active compound content of substantially between 0.0001 to 95% by weight, preferably between 0.0005 to 90% by weight and even more preferably between 0.001 to 75% by weight of the mixture. The composition can also be defined as the ratio of compound to carrier. In the present invention, the weight ratio of these materials (active compound / carrier) may range from 99: 1 to 1: 4, and more preferably from 10: 1 to 1: 3.

Generally, the compounds of this invention dissolve in certain solvents such as acetone, methanol, ethanol, dimethylformamide, pyridine or dimethylsulfoxide, and such solutions can be diluted with water. The concentration of the solution is from 1% to 90% by weight, preferably from 5% to 50% by weight.

• · · ·

For the preparation of emulsifiable concentrates, the compound is dissolved in suitable organic solvents or a mixture of solvents, together with an emulsifying agent, to increase the dispersion of the compound in water. The concentration of the active ingredient in emulsifying concentrates is usually from 10% to 90% by weight and in liquid emulsion concentrates up to 75% by weight.

Suitable sprayable wettable powders are prepared by mixing the compound with finely divided solids such as clays, inorganic silicates and carbonates, and inorganic wetting agents, tackifiers, and / or dispersing agents. The concentration of active ingredients in such formulations is generally within the range of from 20% to 99% by weight, preferably from 40% to 75% by weight. A typical wettable powder is prepared by mixing 50 parts by weight of pyridazinone, 45 parts by weight of synthetically precipitated hydrated silica such as silica sold under the trade name Hi-SilR and 5 parts by weight of sodium lignosulfonate. In another wettable composition, kaolin type (Barden) clay is used instead of Hi-Sil, and another 25% Hi-Sil is replaced by synthetic sodium aluminosilicate, sold under the trade name Zeolex 7.

Dusts are prepared by mixing the compounds of formula (I) or enantiomorphs, salts and complexes thereof with a finely divided inert solid of organic or inorganic origin. Materials useful for this purpose include vegetable flours, silicas and silicates, carbonates and clays. One convenient method of preparing the dust is to dilute the wettable powder with a finely divided carrier. Dust concentrates containing from 20% to 80% by weight of the active ingredient are prepared in a conventional manner and then diluted to 1% to 10% of the concentration used.

• · · · ·

generally used methods such as conventional high-volume liquid sprays, low-volume sprays, ultra-low-volume sprays, air-sprayed sprays, aerial sprays and dusts.

The present invention also contemplates methods of killing, controlling or controlling pests, comprising contacting the pests with a combat or toxic amount (i.e., a pesticidally effective amount) of at least one active compound of the invention, alone or together with a carrier (composition or formulation) as mentioned above. The term contacting, as used in the specification and claims, means applying the active compound of the invention, alone or as a component of a composition or formulation, to at least (a) one such pest and (b) its habitat ) (ie the place to be protected, for example for growing crops or where crops are to be grown).

In addition to the above ingredients, the formulations of this invention may also contain substances generally used in formulations of this kind. For example, a lubricant such as calcium stearate or magnesium stearate may be added to wettable powders or mixtures to be granulated. Further, for example, adhesives such as polyvinyl alcohol cellulose derivatives or other colloidal materials such as casein may be added to improve the adhesion of pesticides to the surface to be protected.

Claims (14)

PATENT CLAIMS A compound of formula I Wherein A is N or CH; V is O or NH; m and n are each independently 0 or 1, provided that m + n is not 2, and U and W are independently O or N; such that when U and W are both N and n is 0 and m is 1, the bond between the 1 and 5 atoms is a double bond and the bond between the _C3-C4 atoms is a single or double bond and when n is 1 and m is 0, a bond between the 2 and 3 atoms there is a double bond and the bond between the C ₄ -C ₆ atoms is a single or a double bond; and that when U is O and W is Nan = m = 0, the bond between the 1 and 5 atoms is a double bond and the bond between the C3-C4 atoms is a single or double bond; and that when U is N and W is Oan = m = 0, the bond between the 2 and 3 atoms is a double bond and the bond between the C ₄ -C ₆ atoms is a single or double bond; X is independently selected from hydrogen, halo, (C 1 -C 4) alkyl and (C 1 -C 4) alkoxy; R is independently selected from hydrogen, (C 1 -C 12) alkyl, halo (C 1 -C 12) alkyl, (C ₂ -C 8) alkenyl, (C ₂ -C 8) alkynyl, (C 1 -C 12) alkoxy (C 1 -C 12) alkyl, (C 3 -C 2) cycloalkyl, (C 3 -C 2) cycloalkyl (C 1 -C 4) alkyl, aryl, aralkyl. - 57 heterocyclic; and R 1 is independently selected from hydrogen, (C 1 -C 6) alkyl and aryl; and Z is selected from (C 1 -C 6) alkyl, halo (C 1 -C 6) alkyl, (C 6 -C 6) cycloalkyl, (C 6 -C 6) cycloalkyl (C 1 -C 4) alkyl, aryl, aralkyl. Compound of Compound of Compound of Compound of Compound according to claim claim claim claim 1, where 1, where 2, where 3, where 4 or A is CH. A is N. V is O. V is O, NH. 5, wherein the group - ° ^{CH -} V7 H, C (V) OC-Z ' A-OCHa is in the meta k position and R is selected from the group consisting of (C 1 -C 12) alkyl, halo (C 1 -C 12) alkyl, monohalo substituted phenyl, (C 1 -C 6) alkyl substituted phenyl, and trihalo substituted phenyl. A compound according to claim 6, wherein U and W are N, R 1 is H, n = 1 and m = 0, and the bond between the 2 and 3 atoms is a double bond - 58 A compound according to claim 7, wherein Z is selected from (C 1 -C 4) alkyl, phenyl, 3-halophenyl, 4-haloenyl and 4- (C 1 -C ₄ ) alkylenes. A compound according to claim 8, wherein R is selected from the group consisting of (C 1 -C ₄ ) alkyl, halo (C 1 -C ₄ ) alkyl, phenyl, 2-haloenyl, 3-halophenyl, 4-haloenyl, 2- ( C 1 -C ₄ alkylphenyl, 3- (C 1 -C ₄ ) alkylphenyl and 4- (C 1 -C ₄ ) alkylphenyl. The compound of claim 9, wherein R is selected from the group consisting of 2-fluorophenyl, 3-fluorophenyl and 4-fluorophenyl. A fungicidal composition for controlling, i.e., controlling phytopathogenic fungi, which comprises an agriculturally acceptable carrier and a compound of any one of the preceding claims, wherein the weight ratio of carrier to compound is 99: 1 to 1: 4. The composition of claim 11, wherein the weight ratio of the agriculturally acceptable carrier to the compound is 10: 1 to 1: 3. A method for controlling phytopathogenic fungi, comprising using in place of seed, plant or soil the compound of any one of claims 1 to 10 at a dose of 0.005 to 50 kilograms per hectare. The method of claim 13, wherein the compound is used at a rate of from 0.025 to 10 kg per hectare. 15. A method of controlling insects in an area comprising the application to the area of a compound of claims 1-9 at a dose of from 0.005 to 10 kilograms per hectare. ·· ···· The method of claim 14, wherein the compound is used at a dose of 0.01 to 1 kilogram per hectare.